The overall objective of the proposed research is to provide insights into one of the most fundamental problems in the neurosciences - the physiological basis of learning and memory. There are three broad aspects of this topic that will be investigated. The first aim is to continue to elucidate the mechanisms of synaptic plasticity that underlies short-term sensitization. Of particular interest will be the interaction of multiple second messenger pathways. Specific objectives of this first aim include: 1) identify the second messenger(s) that mediates the 5-HT-induced modulation of the voltage-dependent delayed K+ channel; 2) Determine the contribution of CaMKII to FMRFamide-induced spike narrowing; 3) identify the second messenger mediating the inhibitory effect of FMRFamide on mobilization and characterize its role in sensitization; and 4) Characterize the currents modulated by a sensitizing stimulus. A second major goal is to investigate the unique mechanisms underlying long-term sensitization from two perspectives: its induction and its expression. Specific objectives of this second and third aim include: 1) Determine the role of cAMP in the induction of long-term synaptic plasticity of sensorimotor connections; 2) Determine the time window of the requirement for gene transcription and protein translation; 3) Examine the time course of long-term plasticity at points longer than 24 hr after training; 4) Determine the role of apTBL-1 in long-term synaptic plasticity; 5) Determine the role of TGF-beta and other growth factors in long-term facilitation. The final aim of the proposal examines distributed representations of learning and memory and seeks to determine whether mechanisms for induction, maintenance and expression are shared among different sites. Although a great deal is known about plasticity at the sensorimotor synapse, modification of other sites in the circuit will be investigated in order to understand the full expression of the behavioral modification. Specific objectives of this aim include: 1) Determine the contribution of interneurons to short-term sensitization; 2) Determine the contribution of interneurons to long-term sensitization; 3) Examine the effects of modulatory transmitters; and 4) Examine the ionic mechanisms and possible second messengers involved in the short-and long-term changes in the properties of the interneurons and motor neurons.